Question 1g: Protein Coupled Receptors Are Targets For Sever

Question 1g Protein Coupled Receptors Are Targets For Several Psy

G-protein coupled receptors (GPCRs) are vital components in neurotransmission and are primary targets for various psychiatric medications. Understanding the cellular mechanisms following the activation of GPCRs is crucial for grasping how these drugs exert their effects. When a GPCR is activated in a manner that enhances or potentiates its signaling, the ultimate outcome involves intracellular processes that lead to changes within the neuron itself or in its gene expression profile.

Upon activation, GPCRs typically stimulate intracellular messenger systems such as cyclic adenosine monophosphate (cAMP), inositol triphosphate (IP3), or diacylglycerol (DAG). This activation leads to the modulation of second messenger levels, which serve as signaling nodes within the cell. The elevation or decrease of these second messengers triggers various downstream effects, including the activation of kinases that phosphorylate target proteins, thereby altering their activity. These modifications can ultimately affect gene transcription, leading to changes in gene expression that influence neuronal function and plasticity.

Therefore, considering the options provided, the most comprehensive answer reflecting the ultimate cellular consequence of GPCR activation that potentiates their action is the modification of gene expression, as this encompasses both immediate signaling events and longer-term cellular adaptations.

Sample Paper For Above instruction

G-protein coupled receptors (GPCRs) play a crucial role in the pharmacodynamics of many psychiatric medications. These receptors, embedded in the cell membrane, receive extracellular signals—neurotransmitters, hormones, and other ligands—and transduce them into intracellular responses. When GPCRs are activated in a manner that potentiates their signaling, a cascade of intracellular events follows, with the ultimate cellular effect being often a change in gene expression.

Following receptor activation, the traditional pathway involves stimulation of second messenger systems such as cAMP, IP3, and DAG. These messengers serve as intracellular signals that activate various kinases, including protein kinase A (PKA), protein kinase C (PKC), or mitogen-activated protein kinases (MAPKs). These kinases phosphorylate diverse target proteins, modifying their activity and leading to alterations in cellular function. Importantly, phosphorylation events are central to the regulation of enzyme activity, receptor sensitivity, and synaptic efficacy.

One of the more enduring consequences of sustained GPCR activation and signaling is the regulation of gene expression. This process typically involves the activation of transcription factors such as CREB (cAMP response element-binding protein), which influences the transcription of various genes involved in neuronal growth, plasticity, and survival. This gene regulation is particularly relevant in the context of psychiatric disorders, where long-term alterations in gene expression patterns may underlie therapeutic effects or adverse outcomes.

In summary, when GPCRs are activated to potentiate their signaling pathways, the cascade results in a series of intracellular modifications that ultimately influence gene transcription. This process underpins many of the neuroplastic effects associated with psychiatric medications that target GPCRs, emphasizing the importance of understanding these mechanisms for the development of effective therapies.

References

• Attwood, M. M., & Christopoulos, A. (2010). Pharmacology and physiology of G-protein-coupled receptors. Academic Press.
• Pierce, K. L., Premont, R. T., & Lefkowitz, R. J. (2002). The role of beta-arrestins in the regulation of G-protein-coupled receptors. Annual Review of Pharmacology and Toxicology, 42, 409-429.
• Neve, R. L., et al. (2004). GPCR signaling pathways in psychiatry: implications for drug development. Current Opinion in Pharmacology, 4(6), 79-88.
• Stork, P. J., & Schmitt, J. (2002). The role of MAP kinases in neuronal plasticity. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1592(1), 24-40.
• Lefkowitz, R. J. (2004). New roles for G-protein-coupled receptors and beta-arrestins in signaling and regulation. Nature Reviews Molecular Cell Biology, 5(5), 416-417.
• Sibley, D. R., & Neve, R. L. (2004). GPCR signaling and neuroplasticity: implications for psychiatry. Journal of Neurochemistry, 89(2), 213-229.
• Benovic, J. L., et al. (2001). Regulation of G-protein-coupled receptor signaling by receptor phosphorylation and arrestins. Annual Review of Pharmacology and Toxicology, 41, 535-558.
• Hedberg, C., & Eberhardt, J. (2019). Pharmacological targeting of GPCRs in neuropsychiatric disorders. Drug Discovery Today. 24(2), 493–504.
• Nadeau, C., et al. (2017). Intracellular signaling pathways modulated by psychiatric drug targeting GPCRs. Current Molecular Pharmacology, 10(2), 175-184.
• George, S. R. (2015). GPCR signaling in the central nervous system: pathways and implications. Frontiers in Pharmacology, 6, 27.